Divinyl ether

Last updated
Divinyl ether
Vinyl ether.svg
Names
Preferred IUPAC name
(Ethenyloxy)ethene
Other names
divinyl ether, divinyl oxide, ethenoxyethene, vinyl ether
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.003.383 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 203-720-5
KEGG
PubChem CID
UNII
UN number 1167
  • InChI=1S/C4H6O/c1-3-5-4-2/h3-4H,1-2H2
    Key: QYKIQEUNHZKYBP-UHFFFAOYSA-N
  • O(\C=C)\C=C
Properties
O(CH=CH2)2
Molar mass 70.091 g·mol−1
Appearancecolorless liquid or gas
Melting point −101 °C (−150 °F; 172 K)
Boiling point 28.3 °C (82.9 °F; 301.4 K)
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
flammable
NFPA 704 (fire diamond)
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 4: Will rapidly or completely vaporize at normal atmospheric pressure and temperature, or is readily dispersed in air and will burn readily. Flash point below 23 °C (73 °F). E.g. propaneInstability 2: Undergoes violent chemical change at elevated temperatures and pressures, reacts violently with water, or may form explosive mixtures with water. E.g. white phosphorusSpecial hazards (white): no code
2
4
2
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Divinyl ether is the organic compound with the formula O(CH=CH2)2. It is a colorless, volatile liquid that has mainly been of interest as an inhalation anesthetic. It is prepared by treating bis(chloroethyl) ether with base. [1]

Contents

History

The analytical techniques used to study its pharmacology laid the groundwork for the testing of new anesthetic agents. Vinyl ether was first prepared in 1887 by Semmler from its sulfur substituted analogue, divinyl sulfide (obtained from the essential oil of Allium ursinum L.), by reaction with silver oxide. In 1899, Knorr and Matthes obtained low yields of vinyl ether by exhaustive methylation of morpholine. [2]

Cretcher et al. reported, in 1925, what would become the foundation for one industrial method used to produce vinyl ether. It was stated that the action of heated sodium hydroxide upon β,β`-dichlorodiethyl ether produced a liquid boiling at 39 °C (among other identified products). [2] However, in a subtly modified process Hibbert et al. reported the isolation of a product boiling at 34-35 °C, "divinyl ether". Finally, in 1929, a patent issued to Merck & Co reported isolation of vinyl ether boiling ca. 28 °C. The currently accepted boiling point of vinyl ether is 28.3 °C; the Merck patent, therefore, was the first to report the isolation of a pure product.

Even before its isolation and characterization, the application of an unsaturated ether as an anesthetic interested some pharmacologists. One such pharmacologist, Chauncey Leake, was particularly captivated by the then theoretical vinyl ether. Leake predicted that vinyl ether would combine the properties of two anesthetic agents, ethyl ether, and ethylene. [3]

As an anesthetic ethylene has many favorable properties, although its very low potency often requires hypoxic conditions to achieve full anesthesia. Ethyl ether, on the other hand, is a relatively potent anesthetic but falls short of ethylene in some respects. In comparison to ether, ethylene has a much lower occurrence of post operative nausea; additionally, ethylene has faster induction and recovery times than ether. [4]

Solely guided by predictions based upon structure, Leake pursued the usage of vinyl ether as an inhalation anesthetic. [5] As vinyl ether was unknown in its pure form, Leake approached organic chemists at Berkeley asking them to synthesize this novel anesthetic. [3] Leake's colleagues however, were unable to prepare vinyl ether; later though, Leake received help from two Princeton chemists, Randolph Major and W. T. Ruigh. [6] Using samples received from Princeton, in 1930, Leake and fellow researcher Mei-Yu Chen published a brief study characterizing the anesthetic effects of vinyl ether upon mice. In the conclusion of this study, they cordially invited further research of this drug. [3]

This invitation was accepted; in 1933 Samuel Gelfan and Irving Bell of the University of Alberta published the first human trials of vinyl ether. They reported the experience of Gelfan himself as he was anesthetized with vinyl ether via the open drop technique. [5] Although, according to Leake, anesthesiologist Mary Botsford at the University of California was the first to clinically administer vinyl ether for a hysterectomy in early 1932. [3]

Thenceforth, vinyl ether was studied extensively at other institutions, though political climate at Berkeley hindered further study by Leake. Vinyl ether had some success but its usage was limited by concerns of liver toxicity and degradation upon long-term storage. [3]

Properties

Vinyl ether is a rather unstable compound which with exposure to light or acid decomposes to acetaldehyde and polymerizes into a glassy solid. Like many other ethers, vinyl ether is also liable to form peroxides upon exposure to air and light. For these reasons vinyl ether is sold with inhibitors such as polyphenols and amines to quell polymerization and peroxide formation. [7] The anesthetic product was inhibited with .01% phenyl-α-napthylamine which gave it a faint violet fluorescence. [8]

Vinyl ether rapidly decolorizes a solution of bromine in carbon tetrachloride; it is also rapidly oxidized by aqueous potassium permanganate; sulfuric acid reacts with vinyl ether producing a black tarry resin and some acetaldehyde. [2]

Anesthetic

In the United States, vinyl ether was sold under the trade name Vinethene. In addition to the normal inhibitors, vinyl ether intended for anesthetic use contained some ethanol (1.5-5%) to prevent frosting of the anesthetic mask. [7] Despite inhibitors manufacturers warned that once opened vinyl ether should be used quickly. [9]

Vinyl ether has a rapid onset with little excitement upon induction. Induction causes little coughing however it produces increased salivation. [8] During anesthesia vinyl ether can cause some patients to twitch. In rare cases this twitching can lead to convulsions; these convulsions are treatable. [10] Additionally, morphine-atropine pre-medication usually prevents this problem. [8] The recovery from vinyl ether is rapid with only rare cases of post operative nausea and vomiting, although headache after anesthesia sometimes occurs. [8]

Short operations pose little danger to the patient. Longer operations which use greater than 200 mL of anesthetic can be dangerous due to hepatic and renal toxicity. In an attempt to circumvent the toxicity of vinyl ether while maintaining its favorable properties it was mixed 1:4 with ethyl ether producing ‘Vinethene Anesthetic Mixture’ (V.A.M.). V.A.M. shows smoother induction and recovery than ethyl ether alone yet is relatively non-toxic for longer procedures. [8] Though compared to ethyl ether V.A.M is less suitable for cases requiring deep anesthesia. [10]

Vinyl ether is a potent anesthetic giving it a large safety margin; the ratio of the anesthetic to lethal dose for vinyl ether is 1 to 2.4 (ethyl ether: 1:1.5). [11] However, this potency is hard to control with simplistic equipment. While anesthetic machines were numerous during the years of vinyl ether's popularity, the simplistic ‘open drop technique’ also maintained its prevalence. Anesthetic machines of the time could suitably contain vinyl ether's potency, however, via the open drop technique smooth anesthesia for long procedures was hard to sustain. [10] Further aggravating this problem, warm temperatures increase the volatility of vinyl ether making it even harder to regulate via the open drop technique. [9]

Overall, vinyl ether's only strengths compared to ethyl ether are favorable induction and recovery. During anesthesia vinyl ether has no particularly wonderful properties and is harder to control than other agents. Therefore, vinyl ether was commonly used as a preliminary anesthetic before administration of diethyl ether. Additionally, vinyl ether was only used for short operations or analgesia, e.g. dentistry and obstetrics. Vinyl ether was used infrequently for long operations because of toxicity, cost, and superior alternatives.

Also, experiments were conducted with ethyl vinyl ether, a compound with one vinyl and one ethyl group. This substance produced results placing it between diethyl ether and divinyl ether both in terms of toxicity and speed of induction and recovery, producing promising results similar to V.A.M. [12] Despite much simpler synthesis (vinylization of ethanol with acetylene) ethyl vinyl ether didn't enter widespread use in anesthetics, as superior halogenated ethers replaced it shortly after its first trials.

Many divinyl ether derivatives of fatty acids exist in nature. [13]

Further reading

Related Research Articles

<span class="mw-page-title-main">Ethanol</span> Organic compound (CH₃CH₂OH)

Ethanol is an organic compound with the chemical formula CH3CH2OH. It is an alcohol, with its formula also written as C2H5OH, C2H6O or EtOH, where Et stands for ethyl. Ethanol is a volatile, flammable, colorless liquid with a characteristic wine-like odor and pungent taste. As a psychoactive depressant, it is the active ingredient in alcoholic drinks, and the second most consumed drug globally behind caffeine.

Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated as MeCHO. It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.

<span class="mw-page-title-main">Chloroethane</span> Chemical compound commonly known as ethyl chloride

Chloroethane, commonly known as ethyl chloride, is a chemical compound with chemical formula CH3CH2Cl, once widely used in producing tetraethyllead, a gasoline additive. It is a colorless, flammable gas or refrigerated liquid with a faintly sweet odor.

<span class="mw-page-title-main">Trichloroethylene</span> C2HCl3, widely used industrial solvent

Trichloroethylene (TCE) is a halocarbon with the formula C2HCl3, commonly used as an industrial degreasing solvent. It is a clear, colourless, non-flammable, volatile liquid with a chloroform-like pleasant mild smell and sweet taste. Its IUPAC name is trichloroethene. Trichloroethylene has been sold under a variety of trade names. Industrial abbreviations include TCE, trichlor, Trike, Tricky and tri. Under the trade names Trimar and Trilene, it was used as a volatile anesthetic and as an inhaled obstetrical analgesic. It should not be confused with the similar 1,1,1-trichloroethane, which is commonly known as chlorothene.

<span class="mw-page-title-main">Ethylene oxide</span> Cyclic compound (C2H4O)

Ethylene oxide is an organic compound with the formula C2H4O. It is a cyclic ether and the simplest epoxide: a three-membered ring consisting of one oxygen atom and two carbon atoms. Ethylene oxide is a colorless and flammable gas with a faintly sweet odor. Because it is a strained ring, ethylene oxide easily participates in a number of addition reactions that result in ring-opening. Ethylene oxide is isomeric with acetaldehyde and with vinyl alcohol. Ethylene oxide is industrially produced by oxidation of ethylene in the presence of a silver catalyst.

<span class="mw-page-title-main">Isoflurane</span> General anaesthetic given via inhalation

Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia, due to airway irritation with isoflurane. Isoflurane is given via inhalation.

<span class="mw-page-title-main">Sevoflurane</span> Inhalational anaesthetic

Sevoflurane, sold under the brand name Sevorane, among others, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset. While its offset may be faster than agents other than desflurane in a few circumstances, its offset is more often similar to that of the much older agent isoflurane. While sevoflurane is only half as soluble as isoflurane in blood, the tissue blood partition coefficients of isoflurane and sevoflurane are quite similar. For example, in the muscle group: isoflurane 2.62 vs. sevoflurane 2.57. In the fat group: isoflurane 52 vs. sevoflurane 50. As a result, the longer the case, the more similar will be the emergence times for sevoflurane and isoflurane.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Desflurane</span> Chemical compound

Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane, and isoflurane, it is a racemic mixture of (R) and (S) optical isomers (enantiomers). Together with sevoflurane, it is gradually replacing isoflurane for human use, except in economically undeveloped areas, where its high cost precludes its use. It has the most rapid onset and offset of the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood.

<span class="mw-page-title-main">Diethyl ether</span> Organic chemical compound

Diethyl ether, or simply ether, is an organic compound with the chemical formula (CH3CH2)2O, also written as C4H10O or (C2H5)2O, sometimes abbreviated as Et2O. It is a colourless, highly volatile, sweet-smelling, extremely flammable liquid. It belongs to the ether class of organic compounds. It is commonly used as a solvent in laboratories and as a starting fluid for some engines. It was formerly used as a general anesthetic, until non-flammable drugs were developed, such as halothane. It has been used as a recreational drug to cause intoxication.

<span class="mw-page-title-main">Inhalational anesthetic</span> Volatile or gaseous anesthetic compound delivered by inhalation

An inhalational anesthetic is a chemical compound possessing general anesthetic properties that is delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporiser and an anesthetic delivery system. Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon.

Glycol ethers are a class of chemical compounds consisting of alkyl ethers that are based on glycols such as ethylene glycol or propylene glycol. They are commonly used as solvents in paints and cleaners. They have good solvent properties while having higher boiling points than the lower-molecular-weight ethers and alcohols.

<span class="mw-page-title-main">Ethylamine</span> Chemical compound

Ethylamine, also known as ethanamine, is an organic compound with the formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscible with virtually all solvents. It is a nucleophilic base, as is typical for amines. Ethylamine is widely used in chemical industry and organic synthesis.

Methoxypropane, or methyl propyl ether, is an ether once used as a general anaesthetic. It is a clear colorless flammable liquid with a boiling point of 38.8 °C.

Guedel's classification is a means of assessing the depth of general anesthesia introduced by Arthur Ernest Guedel (1883–1956) in 1920.

<span class="mw-page-title-main">Flurothyl</span> Chemical compound

Flurothyl (Indoklon) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, but having the opposite effects, acting as a stimulant and convulsant. A clear and stable liquid, it has a mild ethereal odor whose vapors are non-flammable. It is excreted from the body by the lungs in an unchanged state.

Isopropyl alcohol is a colorless, flammable organic compound with a pungent alcoholic odor.

Methyl vinyl ether is an organic compound with the chemical formula CH3OCH=CH2. A colorless gas, it is the simplest enol ether. It is used as a synthetic building block, as is the related compound ethyl vinyl ether (a liquid at room temperature).

<span class="mw-page-title-main">Fluroxene</span> Chemical compound

Fluroxene, or 2,2,2-trifluoroethyl vinyl ether, is a volatile, inhalational anesthetic. It was synthesized in 1951, and was introduced for clinical use in 1954, but was voluntarily withdrawn from the market in 1974 due to its potential flammability and accumulating evidence that it could cause organ toxicity. In any case, prior to being discontinued, it had largely been superseded by halothane. Fluroxene is metabolized to 2,2,2-trifluoroethanol, a compound responsible for some of the toxicity seen with fluroxene use.

<span class="mw-page-title-main">Ethyl vinyl ether</span> Chemical compound

Ethyl vinyl ether is an organic compound with the chemical formula CH3CH2OCH=CH2. It is the simplest enol ether that is liquid at room temperature. It is used as a synthetic building block and a monomer.

References

  1. ↑ Wollweber, Hartmund (2000). "Anesthetics, General". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_289. ISBN   978-3527306732.
  2. 1 2 3 R. Major, et al. U.S. Patent 2,021,872, 1935
  3. 1 2 3 4 5 Mazurek, M J. California Society of Anesthesiologists Bulletin2007, 55(4), 86-9.
  4. ↑ McIntosch. The American Journal of Nursing1925, 25(4), 290-93
  5. 1 2 "New Kind of Ether Acts Faster; Recovery Is Easier" (PDF). Science News Letter. 26 (709): 293–294. 1934-11-10. doi:10.2307/3909877. ISSN   0096-4018. Archived from the original on 2024-02-16.
  6. ↑ Ruigh, William L.; Major, Randolph T. (1931). "The Preparation and Properties of Pure Divinyl Ether". Journal of the American Chemical Society. 53 (7): 2662–2671. doi:10.1021/ja01358a030.
  7. 1 2 R. Major, et al. U.S. Patent 2,099,695, 1937
  8. 1 2 3 4 5 Finer, Basil. Br. J. Anaesthesiol.1965, 37, 661-66
  9. 1 2 Stumpf, E H. The Journal of American Institute of Homeopathy1935, 28(9)
  10. 1 2 3 Martin, Stevens. Anesthesiology1941, 2(3), 285-299
  11. ↑ Anderson L. F. The American Journal of Nursing1937, 37(2), 276-280
  12. ↑ Grosskreutz, Doris C.; Davis, David A. (1956). "Use of ethyl vinyl ether for general and thoracic surgery". Canadian Anaesthetists' Society Journal. 3 (4): 316–325. doi: 10.1007/BF03015275 .
  13. ↑ Alexander N. Grechkin (2002). "Hydroperoxide lyase and divinyl ether synthase". Prostaglandins & Other Lipid Mediators. 68–69: 457–470. doi:10.1016/S0090-6980(02)00048-5. PMID   12432936.
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